The proposed studies will investigate the cortico-cortical structure in the primary somatosensory cortex (SI) of normal animals (cats and primates) and enable a direct comparison in the same brain of cortical connectivity patterns with evoked functional activity. The relationships between structure and function will also be evaluated in states which disrupt neurotransmitter input to the cortex and are known to mimic human diseases which effect cognitive function. The neurotransmitter system chosen for study are implicated in playing a role in sensory cortical processing and include: the adrenergic, the cholinergic and the GABAergic. The first phase of experimentation will establish patterns of cortico-cortical connectivity in SI (comprised of cytoarchitectonic areas 3a, 3b, 1 and 2) through the use of anterograde and retrograde tracers. The labeling patterns will be produced by small injections of tracers into physiologially identified regions of somatosensory cortex. After the anatomical patterns are established, the second phase of study will investigate the relationship between the cortico-cortical connections and functional activity (as determined by 2-deoxyglucose labeling). It is expected that both within and between cytoarchitectonic fields, the locations of the cortico-cortical connections and the evoked metabolic activity produced by appropriate stimuli will be highly correlated. The third phase of study will evaluate the stimulus-evoked metabolic activity produced following manipulations which are known to disrupt the cortical supply of specific neurotransmitters. The manipulations will take the form of either surgical/chemical lesions or pharmacologic treatment with agonists or antagonists of the neurotransmitters. Finally, the cortico-cortical structural relationships and the stimulus-evoked 2-deoxyglucose labeling will be ascertained under the manipulated conditions. It is anticipated that in the altered conditions, the correspondence between cortico-cortical structure and functional activity revealed with 2-deoxyglucose will be less rigid than in the normal animals. Instead the effect changing the cortical modulatory influence of specific neurotransmitters should be strongly reflected in alterations in the metabolic pattern and weakly reflected, if at all, in the intrinsic cortico-cortical connections.